There are a multitude of ways we’re told that could help us to live longer – exercise regularly, eat a healthy diet, minimize stress. A new study in roundworms has instead taken a more molecular approach and found that controlling “jumping genes” could be the key to extending lifespan.
“Jumping genes” are also known as transposable elements (TEs), which are regions of DNA that can move around the genome; in humans, almost half of the genome is made up of TEs. Whilst they’re not always destructive, TEs can often introduce mutations into otherwise functional regions of DNA, and this kind of genomic instability is one of the hallmarks of aging.
In previous research, scientists identified a molecular pathway that appeared to control TEs, known as the Piwi-piRNA system, having seen it at work in so-called “immortal” cells – such as cancer cells, which continue to grow and divide despite genomic instability – and the “immortal jellyfish”. They turned to the common model organism, Caenorhabditis elegans (a species of roundworm), to prove that controlling this pathway, and in turn, the activity of TEs, could increase lifespan.
They found that by activating the Piwi-piRNA system and consequently blocking TE activity, the roundworms used in the study lived between one to four days longer than those where activity wasn’t blocked. The impact was also cumulative – when multiple TEs were controlled, lifespan increased even more.
“In our lifespan assays, by merely downregulating TEs or somatically overexpressing the Piwi-piRNA pathway elements, we observed a statistically significant lifespan advantage,” Ádám Sturm, one of the study’s authors, explained in a statement.
Not only did this provide evidence that the Piwi-piRNA system is indeed involved in regulating TEs, but also confirmed the researchers’ hypothesis that TEs are yet another factor contributing to lifespan. “This opens the door to a myriad of potential applications in the world of medicine and biology,” said Sturm.
The team also found that, as the worms aged, their TEs underwent a series of epigenetic modifications; these are changes that don’t alter the DNA sequence itself but can affect whether genes are expressed or not. As the roundworms aged, methyl groups (one carbon atom and three hydrogen atoms) were attached to their DNA and as a result, there was an increase in TE expression and jumping.
Tibor Vellai, another of the study’s authors, concluded that this discovery could provide the foundations for a pretty useful tool: “This epigenetic modification may pave the way for a method to determine age from DNA, providing an accurate biological clock.”
So whilst TEs might be making us older, it seems they’re also giving us a better idea than ever of how aging works and how we might be able to put a pin in it, too.
The study is published in Nature Communications.
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